Our pediatric GCRC provides inpatient & outpatient & laboratory facilities for the faculty of the University of Pittsburgh School of Medicine to conduct investigations related to disorders of infancy, childhood & adolescence. The GCRC provides a valuable resource for the training of physicians & medical students in clinical investigation, & becomes the stimulus to direct outstanding young physicians toward a career in clinical research. For more than 2 decades, there have been extensive investigations of children with insulin dependent diabetes mellitus (IDDM), that have resulted in major contributions to the field. Future studies will concentrate on characterizing, at the molecular level, factors that identify the genetic susceptibility & confirm a possible viral etiology of IDDM. Also, epidemiologic methods will be used to seek other environmental causes. Techniques with possible improved sensitivity in detecting damaged beta cells, will be explored to attempt to identify those individuals at risk for developing clinical Type I IDDM or diabetes in patients with cystic fibrosis. Studies aimed at identifying risk factors for the development of complications of IDDM will continue, with the evaluation of cognitive dysfunction during hypo & hyperglycemia being a new endeavor. Substantial progress in delineating the relationship between airway inflammatory disease & airway pathophysiology concentrating on allergic & infectious causes have continued. Studies in this proposal represent our extension of research into the role of immune mechanisms in the pathogenesis of respiratory & middle ear disease. Also studies into gastroesophageal reflux in infancy & exercise tolerance & pulmonary function in cystic fibrosis will be continued & expanded. Several other areas of investigation that continue to require the GCRC include: 1) Evaluation of standard therapies for middle ear disease; 2) Pathogenesis of juvenile Graves' Disease; 3) Management of precocious puberty; 4) The evaluation of children with short stature due to psychosocial dwarfism, hypopituitarism & idiopathic short stature. There are several new areas of investigation, including) desferioxamine treatment in children with neuroblastoma; 2) characterization of electrophysiologic CNS maturation in infancy; 3) state-of-the-art investigation into carbohydrate metabolism and growth hormone deficiency & treatment; 4) investigation of neurotransmitters in the pathogenesis of eating disorders. With this renewal application, we request continuing support for the 5 year period, 1990-1995, with an increase from a 4 to 5 bed unit.